The use of extended half-life factor replacement recombinant factor VIII-Fc (rFVIIIFc) and factor IX-Fc (rFIXFc) fusion proteins was effective for managing hemostasis during minor and major surgeries in pediatric and adult patients with hemophilia A and B, according to an analysis of phase III studies. Findings from the analysis were published in Research and Practice in Thrombosis and Haemostasis.
Lead author Pratima Chowdary, MBBS, MD, of the Royal Free Hospital in London, said the analysis represents “the first aggregate data set across a few trials” that explores the role of rFVIIIFc and rFIXFc in perioperative hemostasis management in patients with hemophilia. She also noted these data “highlight the drugs are effective but also highlight the variability” on the use of these agents in real-world clinical practice.
The study included prospectively collected surgical data from the phase III A-LONG/Kids A-LONG or B-LONG/Kids B-LONG studies and their extension studies, ASPIRE or B-YOND. The A-LONG and B-LONG studies included male patients with previously treated severe hemophilia A or B. The corresponding pediatric Kids A-LONG and Kids B-LONG studies included patients under 12 years of age. All patients who completed these studies were eligible to enter the ASPIRE and B-YOND trials.
Major surgeries were performed in 31 patients with hemophilia A in the A-LONG, Kids A-LONG, and ASPIRE studies, and in 22 patients with hemophilia B in the B-LONG, Kids B-LONG, and B-YOND studies. Minor surgeries were performed in 70 patients with hemophilia A in the A-LONG, Kids A-LONG, and ASPIRE trials, and 37 patients with hemophilia B in the B-LONG, Kids B-LONG, and B-YOND studies.
Surgical periods started with the first preoperative dose of rFVIIIFc or rFIXFc and ended before the first regular prophylactic dose. The rFVIIIFc and rFIXFc doses were administered as bolus injections.
The efficacy outcomes for surgical interventions were rFVIIIFc or rFIXFc dosing, the number of injections to maintain hemostasis during surgery, total estimated blood loss in major surgeries, and number of surgeries that required blood transfusion. Additionally, safety endpoints included inhibitor development and adverse events for major surgeries.
The most common major orthopedic procedure across studies was unilateral knee arthroplasty. The median total dose of rFIXFc on the day of surgery was 144 IU/kg, and the median total dose for rFVIIIFc was 81 IU/kg. Most of the major surgeries performed across studies required two or fewer injections, while most major interventions required one or no injections per day on days one through 14.
Approximately 83% of the 84 minor procedures with available data on perioperative rFVIIIFc administration reported one injection to maintain hemostasis. Most of the major surgeries (86%) also reported a single injection of rFVIIIFc to maintain hemostasis. Similar findings were reported for rFIXFc dosing during major surgery (83% with a single injection) and minor surgery (74% with a single injection).
In 42 evaluable major surgeries, hemostasis was rated “excellent” in approximately 93% of interventions. An “excellent” rating was defined as intraoperative and postoperative blood loss that was comparable to a patient without hemophilia. Hemostasis in the remaining 7% of surgeries was rated as “good.” Additionally, all minor surgeries that included a hemostatic assessment were rated as either “excellent” (85%) or “good” (15%).
According to the investigators, there were no major treatment-related safety concerns across analyzed studies. In addition, none of the patients in the studies developed inhibitors or experienced serious vascular thromboembolic events.
The researchers wrote that a potential limitation of the analysis was the variation across practices regarding individualized treatment approaches.
Dr. Chowdary noted that in addition to considering any study limitations, there is also a need to collect real-world data regarding procedures, outcomes, and factor levels in relation to management of perioperative hemostasis in hemophilia, as this may “inform more sophisticated guidelines” on the topic.
Any conflicts of interest declared by the authors can be found in the original article.
Chowdary P, Holmström M, Mahlangu JN, et al. Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc: data on safety and effectiveness from phase 3 pivotal studies. Res Pract Thromb Haemost. 2022;6(5):e12760.